Articles tagged as "Côte d'Ivoire"

How can we improve the UNAIDS modes of transmission model?

The HIV modes of transmission model: a systematic review of its findings and adherence to guidelines.

Shubber Z, Mishra S, Vesga JF, Boily MC. J Int AIDS Soc. 2014 Jun 23;17:18928. doi: 10.7448/IAS.17.1.18928. eCollection 2014.

Introduction: The HIV Modes of Transmission (MOT) model estimates the annual fraction of new HIV infections (FNI) acquired by different risk groups. It was designed to guide country-specific HIV prevention policies. To determine if the MOT produced context-specific recommendations, we analyzed MOT Results by region and epidemic type, and explored the factors (e.g. data used to estimate parameter inputs, adherence to guidelines) influencing the differences.

Methods: We systematically searched MEDLINE, EMBASE and UNAIDS reports, and contacted UNAIDS country directors for published MOT Results from MOT inception (2003) to 25 September 2012.

Results: We retrieved four journal articles and 20 UNAIDS reports covering 29 countries. In 13 countries, the largest FNI (range 26 to 63%) was acquired by the low-risk group and increased with low-risk population size. The FNI among female sex workers (FSWs) remained low (median 1.3%, range 0.04 to 14.4%), with little variability by region and epidemic type despite variability in sexual behaviour. In India and Thailand, where FSWs play an important role in transmission, the FNI among FSWs was 2 and 4%, respectively. In contrast, the FNI among men who have sex with men (MSM) varied across regions (range 0.1 to 89%) and increased with MSM population size. The FNI among people who inject drugs (PWID, range 0 to 82%) was largest in early-phase epidemics with low overall HIV prevalence. Most MOT studies were conducted and reported as per guidelines but data quality remains an issue.

Conclusions: Although countries are generally performing the MOT as per guidelines, there is little variation in the FNI (except among MSM and PWID) by region and epidemic type. Homogeneity in MOT FNI for FSWs, clients and low-risk groups may limit the utility of MOT for guiding country-specific interventions in heterosexual HIV epidemics.

 Abstract  Full-text [free] access

Editor’s notes: In 2002, the HIV Modes of Transmission model (MoT) was developed by UNAIDS to inform and focus, country-specific HIV prevention policies. The idea behind the model was to use simple mathematical modelling approaches, in combination with country specific data, to predict what the distribution of new HIV infection may look like. In this way, countries would be able to better focus their HIV response. Since its development and through 2012, the MoT has been applied in 29 countries, with the findings being used in many settings to shape priorities. In this study, the authors assess the degree to which the MoT produces different outputs in different epidemic contexts. They explore whether there are key parameters in the model that seem to drive similarities and/or differences in projections between countries. Surprisingly, across a broad range of epidemic settings, they found limited variability in the predicted annual fraction of new HIV infections (FNI) acquired by female sex workers (FSW) (0.04-14.4%). There were higher levels of variability between countries in the projected fraction of new HIV infections among men who have sex with men (0.01-89%) and people who inject drugs (0-82%).

The differences in the MoT projections were largely dependent on whether the country in question was categorised as having a concentrated / low-level epidemic, versus generalised epidemic, as defined by UNAIDS. Differences also arose depending upon whether ‘low risk groups’ were also included in the model. Indeed, for 22 of the 25 studies that included a low-risk group, this group was predicted to have a large annual fraction of new HIV infections (11.8-62.9%). This phenomenon arose, not because of high transmission rates in this group (in comparison to others such as MSM or PWIDs) but because these ‘low risk groups’ are large. They are one third of the total population. These findings may be misleading, as the projected high fraction of transmission is dependent on the assumption that everyone in this ‘low risk group’ does have some risk.

It appears that although the MoT was designed to address an important need, it is likely to have limited utility to guide programming in heterosexually driven epidemics.  To address this limitation, UNAIDS is supporting the HIV Modelling Consortium in their development of a revised MoT model that takes into better consideration risk categorization, data constraints and programmatic needs. The revised model is currently undergoing field testing and will be available for country use in 2015.

Africa, Asia, Europe, Latin America
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WHO clinical staging misses a significant proportion of antiretroviral therapy eligible individuals

Diagnostic accuracy of the WHO clinical staging system for defining eligibility for ART in sub-Saharan Africa: a systematic review and meta-analysis.

Munthali C, Taegtmeyer M, Garner PG, Lalloo DG, Squire SB, Corbett EL, Ford N, MacPherson P. J Int AIDS Soc. 2014 Jun 12;17:18932. doi: 10.7448/IAS.17.1.18932. eCollection 2014.

Introduction: The World Health Organization (WHO) recommends that HIV-positive adults with CD4 count ≤500 cells/mm3 initiate antiretroviral therapy (ART). In many countries of sub-Saharan Africa, CD4 count is not widely available or consistently used and instead the WHO clinical staging system is used to determine ART eligibility. However, concerns have been raised regarding its discriminatory ability to identify patients eligible to start ART. We therefore reviewed the accuracy of WHO stage 3 or 4 assessment in identifying ART eligibility according to CD4 count thresholds for ART initiation.

Methods: We systematically searched PubMed and Global Health databases and conference abstracts using a comprehensive strategy for studies that compared the Results of WHO clinical staging with CD4 count thresholds. Studies performed in sub-Saharan Africa and published in English between 1998 and 2013 were eligible for inclusion according to our predefined study protocol. Two authors independently extracted data and assessed methodological quality and risk of bias using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) tool. Summary estimates of sensitivity and specificity were derived for each CD4 count threshold and hierarchical summary receiver operator characteristic curves were plotted.

Results: Fifteen studies met the inclusion criteria, including 25 032 participants from 14 countries. Most studies assessed individuals attending ART clinics prior to treatment initiation. WHO clinical stage 3 or 4 disease had a sensitivity of 60% (95% CI: 45-73%, Q=914.26, p<0.001) and specificity of 73% (95% CI: 60-83%, Q=1439.43, p<0.001) for a CD4 threshold of ≤200 cells/mm3 (11 studies); sensitivity and specificity for a threshold of CD4 count ≤350 cells/mm3 were 45% (95% CI: 26-66%, Q=1607.31, p<0.001) and 85% (95% CI: 69-93%, Q=896.70, p<0.001), respectively (six studies). For the threshold of CD4 count ≤500 cells/mm3 sensitivity was 14% (95% CI: 13-15%) and specificity was 95% (95% CI: 94-96%) (one study).

Conclusions: When used for individual treatment decisions, WHO clinical staging misses a high proportion of individuals who are ART eligible by CD4 count, with sensitivity falling as CD4 count criteria rises. Access to accurate, accessible, robust and affordable CD4 count testing methods will be a pressing need for as long as ART initiation decisions are based on criteria other than seropositivity.

Abstract  Full-text [free] access  

Editor’s notes: This study highlights the major shortcomings of WHO clinical staging when identifying antiretroviral therapy (ART) eligible individuals, with decreasing sensitivity of clinical staging for eligibility at higher CD4 thresholds. There remains limited access to CD4 count testing in many settings in sub-Saharan Africa. The individual and public health benefit of earlier ART initiation will not be achieved unless strategies other than WHO clinical staging are implemented. Access to affordable, quality assured CD4 count testing in all ART initiation clinics may never be feasible in the most resource-constrained settings. Universal treatment, removing the need for CD4 count testing, may be the way to ensure that eligible individuals are started on ART in a timely way.

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Integrating HIV, malaria and diarrhoea prevention is far more efficient than vertical programmes

Scaling up integrated prevention campaigns for global health: costs and cost-effectiveness in 70 countries. 

Marseille E, Jiwani A, Raut A, Verguet S, Walson J, Kahn JG. BMJ Open. 2014 Jun 26;4(6):e003987. doi: 10.1136/bmjopen-2013-003987.

Objective: This study estimated the health impact, cost and cost-effectiveness of an integrated prevention campaign (IPC) focused on diarrhoea, malaria and HIV in 70 countries ranked by per capita disability-adjusted life-year (DALY) burden for the three diseases.

Methods: We constructed a deterministic cost-effectiveness model portraying an IPC combining counselling and testing, cotrimoxazole prophylaxis, referral to treatment and condom distribution for HIV prevention; bed nets for malaria prevention; and provision of household water filters for diarrhoea prevention. We developed a mix of empirical and modelled cost and health impact estimates applied to all 70 countries. One-way, multiway and scenario sensitivity analyses were conducted to document the strength of our findings. We used a healthcare payer's perspective, discounted costs and DALYs at 3% per year and denominated cost in 2012 US dollars.

Primary and secondary outcomes: The primary outcome was cost-effectiveness expressed as net cost per DALY averted. Other outcomes included cost of the IPC; net IPC costs adjusted for averted and additional medical costs and DALYs averted.

Results: Implementation of the IPC in the 10 most cost-effective countries at 15% population coverage would cost US$583 million over 3 years (adjusted costs of US$398 million), averting 8.0 million DALYs. Extending IPC programmes to all 70 of the identified high-burden countries at 15% coverage would cost an adjusted US$51.3 billion and avert 78.7 million DALYs. Incremental cost-effectiveness ranged from US$49 per DALY averted for the 10 countries with the most favourable cost-effectiveness to US$119, US$181, US$335, US$1 692 and US$8 340 per DALY averted as each successive group of 10 countries is added ordered by decreasing cost-effectiveness.

Conclusions: IPC appears cost-effective in many settings, and has the potential to substantially reduce the burden of disease in resource-poor countries. This study increases confidence that IPC can be an important new approach for enhancing global health.

Abstract  Full-text [free] access

Editor’s notes: Increasingly governments and policy makers are seeking to identify how to invest resources most effectively, to achieve multiple health and development outcomes. This paper presents a cost-effectiveness analysis of an integrated campaign to prevent diarrhoea, malaria and HIV.  

They developed a model to estimate the cost per disability adjusted life year (DALY) averted by this intervention, across 70 countries with high disease burden, assuming 15% coverage. The authors categorise countries by income level and their opportunity index (i.e. the opportunity to avert DALYs by having a high disease burden). The findings suggest that an integrated prevention campaign (IPC) could cost as little as US$7 per DALY averted in Guinea-Bissau, a low income, high opportunity country. As would be expected, the contribution of the different IPC components varied by country, depending on their relative disease burdens. This suggests that further focusing of activities within countries may further improve efficiency.

The model was also used to consider potential roll out strategies across counties. For this, countries were grouped into blocks of 10, and ordered with increasing incremental-cost effectiveness. The authors suggest that reaching the top 40 countries with IPC, even at just 15% coverage, could achieve far greater health benefits, with a substantially lower budget, than requested under PEPFAR for antiretroviral therapy alone.

This paper provides further evidence of the need for a more integrated approach to improve population health across disease areas.

Africa, Asia, Europe, Latin America
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Pervasive geographic and transportation-related barriers to HIV services use in sub-Saharan Africa

Impact of geographic and transportation-related barriers on HIV outcomes in sub-Saharan Africa: a systematic review.

Lankowski AJ, Siedner MJ, Bangsberg DR, Tsai AC. AIDS Behav. 2014 Feb 23. [Epub ahead of print]

Difficulty obtaining reliable transportation to clinic is frequently cited as a barrier to HIV care in sub-Saharan Africa (SSA). Numerous studies have sought to characterize the impact of geographic and transportation-related barriers on HIV outcomes in SSA, but to date there has been no systematic attempt to summarize these findings. In this systematic review, we summarized this body of literature. We searched for studies conducted in SSA examining the following outcomes in the HIV care continuum: (1) voluntary counseling and testing, (2) pre-antiretroviral therapy (ART) linkage to care, (3) loss to follow-up and mortality, and (4) ART adherence and/or viral suppression. We identified 34 studies containing 52 unique estimates of association between a geographic or transportation-related barrier and an HIV outcome. There was an inverse effect in 23 estimates (44 %), a null association in 26 (50 %), and a paradoxical beneficial impact in 3 (6 %). We conclude that geographic and transportation-related barriers are associated with poor outcomes across the continuum of HIV care.


Editor’s notes: This systematic review focuses on the importance of structural barriers to uptake of HIV treatment and care. Specifically, these are the association between geographic and transportation-related barriers and poor outcomes among HIV positive persons. Most of the quantitative and qualitative evidence reviewed in this paper (from 66 studies in sub-Saharan Africa) support the authors’ hypothesis that geographic and transportation-related barriers contribute to poor outcomes in HIV-positive individuals at all points along the continuum of HIV care. These were indexed in terms of voluntary counselling and testing, pre- antiretroviral therapy linkage to care, loss to follow-up, and adherence and/or viral suppression. A lack of association between these barriers and HIV services use was more common in studies where the study had clear limitations. For example, the use of self-reported as opposed to objective measures of exposures, small sample sizes, and the lack of control for confounding variables. The study has important policy implications related to the decentralisation of HIV treatment and care services, point-of-care services delivery, the provision of transportation stipends, the simplification of management protocols, and the reduction in the frequency of follow up visits.

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CD4 counts at antiretroviral therapy start rising globally, but could do better!

Immunodeficiency at the start of combination antiretroviral therapy in low-,  middle-, and high-income countries.

The IeDEA and ART Cohort Collaborations. J Acquir Immune Defic Syndr 2014 Jan 1;65(1):e8-e16. doi: 10.1097/QAI.0b013e3182a39979.

Objective: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries.

Methods: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed.

Results: In total, 379 865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/µL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/µL (76% increase), 88 to 135 cells/µL (53%), and 209 to 274 cells/µL (31%). In 2009, compared with LIC, median counts were 13 cells/µL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/µL (-62 to +18) lower in UMIC, and 112 cells/µL (+75 to +149) higher in HIC. They were 23 cells/µL (95% CI: +18 to +28 cells/µL) higher in women than men. Median counts were 88 cells/µL (95% CI: +35 to +141 cells/µL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage.

Conclusions: Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/µL in LIC and MIC and below 300 cells/µL in HIC. Earlier start of cART will require substantial efforts and resources globally.

Abstract access 

Editor’s notes: In this multi-cohort analysis spanning six continents, median CD4 counts at initiation of combination antiretroviral therapy were substantially higher in high-income compared to low- or middle-income countries. Median CD4 counts at initiation increased between 2002 and 2009 in most countries studied, but these increases were greater in low- and middle-income than high-income countries and were greater among men than women. Baseline CD4 counts in low- and middle-income countries were higher among countries with national antiretroviral therapy coverage of 80% or above. Nevertheless, despite the massive scale-up of antiretroviral therapy in low-income countries since 2002, the increases in median CD4 count at the start of antiretroviral therapy have been modest. Substantial efforts and resources are needed to achieve earlier implementation of antiretroviral therapy globally.

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Safety of tenofovir during pregnancy

Safety of tenofovir during pregnancy for the mother and fetus: a systematic review.

Wang L, Kourtis AP, Ellington S, Legardy-Williams J, Bulterys M. Clin Infect Dis. 2013 Dec;57(12):1773-81. doi: 10.1093/cid/cit601. Epub 2013 Sep 17.

Tenofovir disoproxil fumarate (TDF) safety during pregnancy has important public health implications. This review summarizes TDF safety during pregnancy, focusing on pregnancy outcomes, congenital anomaly risk, and other potential toxicities on neonates. Although information is limited, TDF appears to be safe during pregnancy. In 6 studies of human immunodeficiency virus type 1 (and/or hepatitis B virus)-infected women receiving TDF during pregnancy, adverse events were mild to moderate; none were considered to be TDF-related. Five studies that followed in utero TDF-exposed infants showed no increased risk of growth or bone abnormalities. One study showed slightly lower infant height at age 1 year, but the significance is unclear. The Antiretroviral Pregnancy Registry database, with 1 800 pregnancies exposed to TDF in the first trimester, does not indicate increased congenital anomaly risk with TDF exposure. More evidence collected prospectively, ideally with bone density measurements and randomized trial design, will be optimal to determine the effects of antenatal TDF exposure on children's health.

Abstract  Full-text [free] access

Editor’s notes: Tenofovir is a well-tolerated antiretroviral drug which is effective against HIV and hepatitis B. Due to these favourable characteristics and its once-daily dosing, tenofovir is increasingly used in clinical practice. As a result, more women are exposed to this drug at conception and during pregnancy. Tenofovir is classified by the US Food and Drug Administration as a pregnancy category B drug. This means that there is insufficient evidence to determine risk in humans. The authors of this paper provide the reader with an updated systematic review of the safety of tenofovir in pregnancy. Amongst the studies looking at adverse events in infants and mothers, no serious adverse events occurred which were attributed to tenofovir. Likewise, no study identified an increased risk of growth or bone abnormalities in infants up to two years of age. These studies need to be interpreted with caution as many studies had small sample sizes and in some studies the duration of exposure to tenofovir was short (single dose-seven days). Arguably, the most reassuring evidence comes from the antiretroviral pregnancy registry database report, which showed no increased risk of congenital anomalies amongst 1 800 infants exposed to tenofovir in utero. This systematic literature review notes the paucity of available evidence to guide decision-making and highlights the need for further studies to determine the risk to humans of tenofovir exposure during pregnancy.

HIV Treatment
Africa, Asia, Europe, Northern America
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Persistent gender inequities in ART uptake and retention in sub-Saharan Africa – strategies needed to better engage men.

Differences Between HIV-Infected Men and Women in Antiretroviral Therapy Outcomes - Six African Countries, 2004-2012.

Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2013 Nov 29;62(47):946-52.

Evaluation of differences between human immunodeficiency virus (HIV)-infected men and women in antiretroviral therapy (ART) enrollment characteristics and outcomes might identify opportunities to improve ART program patient outcomes and prevention impact. During September 2008-February 2012, retrospective cohort studies to estimate attrition of enrollees (i.e. from death, stopping ART, or loss to follow-up) at 6-month intervals after ART initiation were completed among samples of adult men and women (defined as aged ≥15 years or aged ≥18 years) who initiated ART during 2004-2010 in six African countries: Côte d'Ivoire in western Africa; Swaziland, Mozambique, and Zambia in southern Africa; and Uganda and Tanzania in eastern Africa. Records for 13 175 ART enrollees were analyzed; sample sizes among the six countries ranged from 1 457 to 3 682. In each country, women comprised 61%-67% of ART enrollees. Median CD4 count range was 119-141 cells/µL for men and 137-161 cells/µL for women. Compared with women, a greater percentage of men initiated ART who had World Health Organization (WHO) HIV stage IV disease. In cohorts from western Africa and southern Africa, the risk for attrition was 15%-26% lower among women compared with men in multivariable analysis. However, in eastern Africa, differences between men and women in risk for attrition were not statistically significant. Research to identify country-specific causes for increased attrition and delayed initiation of care among men could identify strategies to improve ART program outcomes among men, which might contribute to prevention of new HIV infections in female partners.

Abstract   Full-text [free] access

Editor’s notes: Equitable access to treatment is a widely endorsed principle in all fields of medicine. This study on gender differences in the uptake and outcomes of antiretroviral therapy (ART) provides programme managers with the evidence to assess and possibly rectify any imbalance. The study is based on clinical cohort data from six geographically diverse African countries. The study found that (1) women account for the majority of patients on ART, (2) they are less likely to enrol with advanced HIV disease, and (3) they have lower attrition rates (mortality, loss to follow up, etc.), after adjusting for possible baseline predictors of survival such as the CD4 count. The first of the three findings may be related to higher eligibility rates in women, which is difficult to assess using clinical data alone. It may also be related to the evidence in favour of higher male attrition rates that was not as strong in the two East African sites. We also need to bear in mind that higher attrition may result from causes unrelated to HIV (see Sabin CA in this issue). Aside from these caveats, the results do indeed suggest that greater effort is necessary to engage men in HIV treatment and care programmes.  This will rectify the apparent imbalance in treatment uptake and outcomes, and it will also have implications for onward transmission to their (female) partners. 

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An integrated investment approach for women’s and children’s health

Advancing social and economic development by investing in women's and children's health: a new Global Investment Framework.

Stenberg K, Axelson H, Sheehan P, Anderson I, Gülmezoglu AM, Temmerman M, Mason E, Friedman HS, Bhutta ZA, Lawn JE, Sweeny K, Tulloch J, Hansen P, Chopra M, Gupta A, Vogel JP, Ostergren M, Rasmussen B, Levin C, Boyle C, Kuruvilla S, Koblinsky M, Walker N, de Francisco A, Novcic N, Presern C, Jamison D, Bustreo F; on behalf of the Study Group for the Global Investment Framework for Women's Children's Health. Lancet. 2013 Nov 18. doi: S0140-6736(13)62231-X. pii: 10.1016/S0140-6736(13)62231-X. [Epub ahead of print]

A new Global Investment Framework for Women's and Children's Health demonstrates how investment in women's and children's health will secure high health, social, and economic returns. We costed health systems strengthening and six investment packages for: maternal and newborn health, child health, immunisation, family planning, HIV/AIDS, and malaria. Nutrition is a cross-cutting theme. We then used simulation modelling to estimate the health and socioeconomic returns of these investments. Increasing health expenditure by just $5 per person per year up to 2035 in 74 high-burden countries could yield up to nine times that value in economic and social benefits. These returns include greater gross domestic product (GDP) growth through improved productivity, and prevention of the needless deaths of 147 million children, 32 million stillbirths, and 5 million women by 2035. These gains could be achieved by an additional investment of $30 billion per year, equivalent to a 2% increase above current spending.

Abstract access 

Editor’s notes: Over the past 20 years there have been substantial gains in maternal and child health (MCH). However, much still needs to be done – assuming a continuation of current rates of progress, there would nevertheless be shortfalls in the achievement of MDG 4 and 5 targets. Especially in sub-Saharan Africa, HIV is an important underlying cause of maternal and child ill health. This paper models the costs and benefits of an accelerated action on MCH, including for HIV, the prevention of mother to child HIV transmission; first line treatment for pregnant women; cotrimoxazole for children, and the provision of paediatric antiretroviral therapy (ART). These HIV services are complemented by health systems strengthening; increased family planning provision; and packages for malaria, immunisation, and child health. The paper is interesting for many reasons, including both the breadth of its intervention focus, and the detailed modelling of the likely health, social and economic benefits of such investments.

Although the direct HIV related benefits are not described in detail in the main paper, it is likely that these result both from increased contraceptive use (prong 2 for preventing vertical HIV transmission), as well as ART and cotrimoxazole provision. It also illustrates the potential value of developing a cross-disease investment approach, as a means to ensure that services effectively respond to the breadth of women’s and children’s health needs. This more ‘joined up’, integrated perspective on strategies for health investment can support core investments in health systems strengthening. It can also potentially achieve important cross-disease synergies, e.g., ensuring that a child who has not acquired HIV at birth does not then die from malaria. 

Africa, Asia, Latin America, Oceania
Afghanistan, Angola, Azerbaijan, Bangladesh, Benin, Bolivia, Botswana, Brazil, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Congo, Côte d'Ivoire, Democratic People's Republic of Korea, Democratic Republic of the Congo, Djibouti, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guatemala, Guinea, Guinea-Bissau, Haiti, India, Indonesia, Iraq, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mexico, Morocco, Mozambique, Myanmar, Nepal, Niger, Nigeria, Pakistan, Papua New Guinea, Peru, Philippines, Rwanda, Sao Tome and Principe, Senegal, Sierra Leone, Solomon Islands, Somalia, South Africa, Sudan, Swaziland, Tajikistan, Togo, Turkmenistan, Uganda, United Republic of Tanzania, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
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Highly variable virological outcomes in ART programmes in seven countries

Extraordinary Heterogeneity of Virological Outcomes in Patients Receiving Highly Antiretroviral Therapy and Monitored With the World Health Organization Public Health Approach in Sub-Saharan Africa and Southeast Asia.

Aghokeng AF, Monleau M, Eymard-Duvernay S, Dagnra A, Kania D, Ngo-Giang-Huong  N, Toni TD, Touré-Kane C, Truong LX, Delaporte E, Chaix ML, Peeters M, Ayouba A; for the ANRS 12186 Study Group. Clin Infect Dis. 2013 Oct 23. [Epub ahead of print]

Background:  The limited access to virological monitoring in developing countries is a major weakness of the current antiretroviral treatment (ART) strategy in these settings. We conducted a large cross-sectional study in Burkina Faso, Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess virological failure and drug resistance mutations (DRMs) after 12 or 24 months of ART.

Methods:  Between 2009 and 2011, we recruited adults attending ART centers 10-14 months (the M12 group) or 22-26 months (M24 group) after initiating ART. Demographic and clinical data were collected on site, and viral load was measured. Samples with a viral load of ≥ 1 000 copies/mL, considered as the failure threshold, were genotyped for drug resistance assessment.

Results:  Overall, 3 935 patients were recruited (2 060 at M12 and 1 875 at M24). Median ages varied from 32 to 42 years. Median CD4+ T-cell counts at ART initiation were low (99-172 cells/µL). The main ART regimens included stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was 11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these patients, respectively, had drug-resistant virus. Across sites, virological failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24 patients. Predominant DRMs were associated with ART regimens, but virus in several patients accumulated DRMs to drugs not received, such as abacavir, didanosine, tenofovir, etravirine, and rilpivirine.

Conclusions:  Our findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.

Abstract access 

Editor’s notes: As the number of people taking antiretroviral therapy (ART) increases, more attention will be needed to sustaining programme quality and effectiveness. The proportion of people taking ART who have suppressed HIV viral load is a key measure of treatment success. This survey of ART programmes in seven countries found wide variation in the proportion of patients with HIV viral load ≥1 000 copies per ml. This illustrates the value of viral load monitoring as a measure of programme quality. Among individuals with HIV viral load ≥1 000 copies per ml, most but not all had drug-resistant virus. This illustrates the difficulty of rational management of “treatment failure” where resistance cannot be determined. Of more concern are few patients who had resistance to drugs they apparently had never taken. This underlines the importance of careful ART stewardship to maximize the benefits of ART at population level. 

Africa, Asia
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No evidence of sexual disinhibition with early ART

Effect of early antiretroviral therapy on sexual behaviors and HIV-1 transmission risk in adults with diverse heterosexual partnership status in Cote d'Ivoire.

Jean K, Gabillard D, Moh R, Danel C, Fassassi R, Desgrees-du-Lou A, Eholie S, Lert F, Anglaret X, Dray-Spira R. J Infect Dis. 2013 Aug 29. [Epub ahead of print]

Background:  The effect of early antiretroviral therapy (ART) on sexual behaviors and HIV-1 transmission risk has not been documented beyond the specific population of stable serodiscordant couples.

Methods:  Based on a behavioral study nested in a randomized controlled trial (Temprano-ANRS12136) of early ART, we compared proportions of risky sex (unprotected sex with a partner of negative/unknown HIV status) reported 12 months after inclusion between participants randomized to initiate ART immediately ('early ART') or according to WHO criteria ('standard ART'). Group-specific HIV-transmission rates were estimated based on sexual behaviors and viral load-specific per-act HIV-1 transmission probabilities. Their ratio was computed to estimate the protective effect of early ART.

Results:  Among 957 participants (baseline CD4: 478/mm3), 46.0% reported sexual activity in the past month, 41.5% of them with non-cohabiting partners. Proportion of risky sex was 10.0% vs. 12.8%, respectively, in participants on early vs. standard ART (p=0.17). Accounting for sexual behaviors and viral load, the estimated protective effect of early ART was 90% (95%CI 81-95%).

Conclusion:  Twelve months after inclusion, patients on early and standard ART reported similar sexual behaviors. Early ART decreased the estimated risk of HIV transmission by 90%, suggesting a major prevention benefit among both stable and casual partners.

Abstract Full-text [free] access

Editor’s notes: As interest grows in using ART as treatment and prevention, the effect of early ART on sexual behaviour becomes ever more pertinent. This study in Cote d’Ivoire is nested in a four-arm clinical trial which examines the risks and benefits for individual health of early ART compared with “standard ART”, in combination with and without Isoniazid preventive therapy. A key finding was that there was no difference observed in reported “risky” sex (defined as unprotected sex with a partner who was not already known to be HIV-positive if the index patient had a VL ≥300 copies /mm3). In addition, there was a more complete viral suppression with immediate treatment over the duration of infection. This led to a 90% protective effect from early ART. The observation that 42% of sexually active trial patients had their last sexual encounter with a non-cohabiting partner is a reminder of the limitations of focusing HIV prevention efforts on stable serodiscordant relationships. The authors estimate that 161 infections could be averted per 10 000 patients in the first year by using early vs standard ART. While evidence from large-scale community randomized trials on the effect of treatment as prevention on population level HIV incidence is awaited, the information from this study is encouraging.

Côte d'Ivoire
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